Causal analyses, statistical efficiency and phenotypic precision through Recall-by-Genotype study design

Corbin, LJ; Vy, Tan; Hughes, D.A.; Wade, Kaitlin H; Ds, Paul; Tansey, Katherine E.; Butcher, Frances; Dudbridge, Frank; Howson, JM; Jallow, MW; John, Catherine; Kingston, Nathalie; Cm, Lindgren; O'Donavan, Michael; O’Rahilly, Stephen; Palmer, Cna; Pearson, Ewan R.; Ra, Scott; van, Da Heel; Whittaker, John C.; Frayling, Timothy M.; Tobin, Martin D.; Wain, Louise V.; Dm, Evans; Karpe, Fredrik; McCarthy, M. I.; Danesh, John; Franks, PW; Nj, Timpson

doi:10.1101/124586

Cited by 3 publications

(2 citation statements)

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“…to capture balanced numbers of specific gene variants) and analytical power in a relatively small number of participants as a result of the availability of large pre-genotyped collections. This approach can be effective in dissecting genetic association signals through deep phenotyping in smaller sample sets; it is a cost effective strategy and in the rare variant setting it may be the only feasible approach to recruitment for novel studies or for replication studies [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

The ethics conundrum in Recall by Genotype (RbG) research: Perspectives from birth cohort participants

et al. 2018

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PurposeRecall by genotype (RbG) research recruits on the basis of genetic variation. Increased use of this approach presents an ethical conundrum for cohort studies/biobanks: whether to inform individuals of their genetic information and deviate from standard practice of non-disclosure of results, or mask this information at the level of the individual participant. This paper examines the perspectives of research study participants on RbG research.MethodsFifty-three semi-structured interviews were conducted with young adult participants of the Avon Longitudinal Study of Parents and Children (ALSPAC). Topics included understandings of RbG research, expectations around recruitment and communication of research findings.ResultsParticipants uniformly expressed a deep trust and faith in ALSPAC and considered themselves part of the ALSPAC team. Such perspectives, alongside a limited knowledge of genetics and modest interest in reported research outcomes, meant few participants reported immediate concerns about being recruited by genotype.ConclusionOur findings highlight the responsibility and duty of care on RbG researchers, and longitudinal studies more generally, and the importance of solidarity, reciprocity and co-production in study-participant relations. As such, we consider existing recommendations for conducting RbG research in longitudinal studies in light of our results and speak to recent changes in the approach used by ALSPAC.

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Section: Introductionmentioning

confidence: 99%

The ethics conundrum in Recall by Genotype (RbG) research: Perspectives from birth cohort participants

et al. 2018

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“…The resource includes contemporary measures that reflect current tests and treatments. Longitudinal research is therefore feasible, with mechanisms also in place for re-contact of GS participants for targeted follow-up 11 , including recall-by-genotype studies 12 , enabling detailed research on chronic conditions and long-term outcomes.…”

Section: Methodsmentioning

confidence: 99%

Electronic health record and genome-wide genetic data in Generation Scotland participants

et al. 2017

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This article provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records, in particular, represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets, including cancer, mental health and maternity inpatient information, is also possible through the same straightforward and transparent application process. The EHR linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures, such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genome-wide genetic information.

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Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants

Kerr

Campbell

Marten

et al. 2017

Preprint

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This paper provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records in particular represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets including cancer, mental health and maternity inpatient information is also possible through the same straightforward and transparent application process. The Electronic Health Record linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index (CHI) number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genomewide genetic information.

show abstract

Causal analyses, statistical efficiency and phenotypic precision through Recall-by-Genotype study design

Cited by 3 publications

References 62 publications

The ethics conundrum in Recall by Genotype (RbG) research: Perspectives from birth cohort participants

The ethics conundrum in Recall by Genotype (RbG) research: Perspectives from birth cohort participants

Electronic health record and genome-wide genetic data in Generation Scotland participants

Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants

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